Project Summary The mammalian female reproductive tract, including the oviducts, uterus, and vagina, is essential for the continuation of the species and a frequent site of human disease, including infertility and cancer. The female reproductive tract is derived from the Mllerian ducts of the fetus, a pair of epithelial tubes with a surrounding mesenchyme. In mammals, two pairs of genital ducts form within the mesonephroi associated with the fetal gonads regardless of sex genotype. Initially, the Wolffian ducts form that subsequently give rise to the vas deferentia, epididymides, and seminal vesicles. The Wolffian ducts then guide the formation of the Mllerian ducts. In males, the fetal testes produce the TGF-b family member anti-Mllerian hormone (AMH) that binds receptors expressed in the Mllerian duct mesenchyme, causing the elimination of the Mllerian ducts. The fetal ovaries do not produce AMH, permitting Mllerian duct differentiation. Thus, mammalian fetuses are initially ambi-sexual with the potential to develop both male and female reproductive tract organs. Defects in the formation of the genital ducts and resolution of the ambi-sexual state to a male or female phenotype lead to disorders of sexual development (DSD). Although much progress has been made in understanding the development and differentiation of the female reproductive tract and the elimination of the Mllerian system in the male fetus there are still many fundamental unanswered questions. The primary objective of this proposal is to determine the molecular, cellular, and developmental mechanisms that regulate female reproductive tract organogenesis and its regression during male differentiation.